This invention relates to a pharmaceutical composition for treatment of adult respiratory distress syndrome (ARDS) that contains a human atrial natriuretic peptide (hereunder abbreviated as "h-ANP") as an effective ingredient.
Adult respiratory distress syndrome (ARDS) is the general term for those manifestations of serious respiratory failure which occur in the trachea as a consequence of various predisposing conditions including shock, trauma, fracture, septicemia and drug intoxication. ARDS is characterized by interstitial edematous disorders resulting from enhanced permeability of the pulmonary vascular endothelium and the alveolar epithelium and causes such diseases as pulmonary edema and atelectasis and, in an extreme case, results in irreversible interstitial fibrosis and reduced pulmonary vascular beds. The first phase of ARDS is evidenced by the appearance of dyspnea, and the second phase by hypoxemia and infiltrations on chest X-ray. In the third phase, alveolar disorders proceed and the pulmonary compliance decreases so much as to render the institution of mechanical ventilation mandatory. The mortality rate up to this stage is about 50%; in the fourth phase, pulmonary fibrosis and infection become marked and the mortality rate is as high as about 80%.
One of the methods conventionally adopted to treat ARDS is respiratory management. This involves ventilation (positive end-expiratory pressure, which is hereunder abbreviated as "PEEP") in order to achieve improvements on the loss of pulmonary compliance and residual functional gas. In PEEP, an obstructed peripheral airway is cleared and collapsing alvedi are reinflated, thereby promoting gas exchange. However, as it has turned out, this approach causes two clinical problems, i.e., damage to tile alveolar epithelium and enhanced interstitial edema.
Speaking of drug therapy, there are no drugs available today that are effective against ARDS. Steroids such as prednisolone methyl acetate (Depo-medorole) have been administered in pulse in expectation of their ability to enhance vascular permeation or to suppress the release of proteases; however, those steroids have been shown to have no efficacy against ARDS.
Since it is known that many mediators released from neutrophils, macrophages and platelets take part in the development of ARDS, extensive review has been made of antagonists and synthesis inhibitors including peroxide scavengers such as SOD and vitamin E1, TXA2 synthesis inhibitors such as OKY-046, cycloxygenase inhibitors such as ibuprofen, and protease inhibitors such as urinastatin. However, the mechanism behind the development of ARDS cannot be explained by any single mediator, so none of the reagents studied for far have proved to be completely effective.